Lavendustin C, a natural-product derived anticancer lead compound, was modified at its carboxylic group by esterification or amidation (compounds 6–10) and at its amino group by introducing 5-arylidenethiazolin-4-ones (14a–c to 17a–c, 18a and 18b). Two strategies were used to combine these moieties and to optimize the yield. These new compounds were evaluated for their antiproliferative activities against a panel of nine cancer cell lines. The results clearly show that 5-arylidenethiazolin-4-one moiety contributes substantially to the activity. Also, methyl esters are more potent than amides, while N-ethylamides are the most potent among amides. 14b showed the highest potency against all tested cancer cell lines with IC₅₀ 1.4–2.5 µM, while against normal cell line IC₅₀ > 50 µM. It showed arrest of HeLa cells at G0/G1, S p

This study explores the synthesis of pyrimidine heterocycles 9–29. The exact structure was determined and confirmed by NMR, HRMS, and X-ray diffraction investigation. Compounds 9–29 were evaluated as dual inhibitors of EGFR and VEGFR-2 in order to develop a scaffold capable of stopping cell growth. The findings indicated that compounds 22 and 29 are potential apoptotic antiproliferative agents that inhibit EGFR and VEGFR-2. Molecular docking studies have clearly shown how compounds 22 and 29 bind to the active sites of EGFR and VEGFR-2. This comprehensive examination is essential for comprehending their mechanism of action as antiproliferative agents. Moreover, the in-depth study of these hybrids’ absorption, distribution, metabolism, and excretion (ADME) features shows how useful they could be as therapeutic agents.

Conversely, additional structural modifications may be necessary to effectively obtain more potent lead molecules for the development of future cancer therapeutics.

Bioassay-guided fractionation approach led to identification of two novel compounds; (4-(hydroxymethyl)-3-methoxy-1H-pyrazol (1) and mycalene (2), alongside with four known metabolites; octadecane (3), hexatriacontane (4), 1-heneicosanol (5) and heptatriacontanoic acid (6) from the Red Sea marine sponge Hemimycale sp. The ethyl acetate fraction showed a noticeable cytotoxic activity against the lung cancer cell line (A549) with IC₅₀ value of 75.54 µg/ mL. Structural elucidation was achieved using a combination of 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS). To elucidate the potential mechanism of action behind the cytotoxic effects against lung cancer, a multi-faceted approach combining in silico network pharmacology, experimental validation, and molecular docking studies were employed. Both compounds …

A novel set of quinazoline-4-one/1,2,4-oxadiazole hybrids (9a-o) was designed and synthesized as EGFR, EGFR^T790M, and BRAF^V600E inhibitors in the search for multitargeted antiproliferative scaffold. The novel hybrids showed encouraging antiproliferative actions. Compounds 9b, 9c, 9h, 9k, and 9l were evaluated as EGFR and BRAF^V600E inhibitors. These in vitro experiments demonstrated that compounds 9b, 9c, and 9h are potent antiproliferative agents capable of acting as dual EGFR/BRAF^V600E inhibitors. 9b, 9c, and 9h were further studied for their inhibitory effect on mutant EGFR (EGFR^T790M), with the results indicating that the evaluated compounds had a significant inhibitory effect. Cell cycle analysis and apoptosis induction assay of 9b revealed cell cycle arrest at the G2/M phase, which can induce apoptosis. EGFR and BRAF^V600E docking simulations inside their active regions shed light on these compounds’ possible modes of inhibition. ADME calculations revealed that all test compounds satisfy Lipinski’s rule of five (RO5) with MLogP <5, with easy transport through cell membranes and higher oral bioavailability. These new hybrids may have potential as anti-cancer drugs after optimization.

A novel series of 1,2,3-triazole/quinazoline-4-one hybrids (8a–t) were designed and synthesized as dual-targeted antiproliferative agents. Compounds 8a–t were evaluated for their antiproliferative efficacy against a panel of four cancer cell lines. The results indicated that most of the evaluated compounds exhibited strong antiproliferative activity, with 8f, 8g, 8h, 8j, and 8l demonstrating the highest potency. These five compounds were investigated as EGFR and BRAFV600E inhibitors. The in vitro tests showed that compounds 8g, 8h, and 8j are strong antiproliferative agents that might work as dual EGFR/BRAFV600E inhibitors. Compounds 8g and 8h were further examined as activators of caspases 3, 8, and Bax and down-regulators of the anti-apoptotic protein Bcl2. The results indicated that the studied compounds had considerable apoptotic antiproliferative action. The investigation of the cell cycle and apoptosis …

Chemical investigations of the sea urchin Clypeaster humilis has led to separation of twelve compounds including one new sulfonic acid derivative (7R) tridec-1-en-7-yl hydrogen sulphate (1), first isolated from natural source, pyridine-3-yl methane sulfonate (2), and first isolated from marine organisms, boldine (12), in addition to nine known compounds (3–11), which were isolated for the first time from the genus Clypeaster. Their structures were elucidated based on spectroscopic analyses (1D and 2D NMR), HR-ESI-MS as well as comparison with the previously reported data. The antiviral activity of the crude extract and sulphated compounds were evaluated using MTT colorimetric assay against Coxsackie B4 virus. The crude extract and compound 1 showed very potent antiviral activity with a percentage of inhibition equal to 89.7 ± 0.53% and 86.1 ± 0.92%, respectively. Results of the molecular docking analysis of the isolated compounds within Coxsackie Virus B4 (COX-B4) X-ray crystal structure and quantum chemical calculation for three sulphated compounds are in a consistent adaptation with the in vitro antiviral results. The pharmacokinetic properties (ADME) of isolated compounds were determined.

Background

Lepidium sativum, Garden Cress (GC), seeds have a lot of natural molecules with a pronounced activity against different disorders. It was reported that GC seeds have the ability to lower the blood glucose level.

Aim

The aim of this work was to formulate GC seeds into oral tablets containing a fixed dose of the grounded seeds. Furthermore, the anti-diabetic performance of the prepared tablets was studied in the streptozotocin rats’ model in comparison with positive control metformin.

Methods

Micrometrics of GC grounded seeds with different excipients were investigated. Then, GC tablets were prepared via direct compression technique. GC tablets were characterized for their uniformity of dosage unit, friability, hardness, disintegration time, and in vitro release. The antidiabetic effect was studied in rats for a period of 28 days. Glycosylated hemoglobin, liver performance, and lipid levels include total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also estimated. In addition, histopathological study of liver and pancreas was also performed.

Results

Prosolv^®EasyTab produced tablets with higher hardness, lower disintegration time, and fast release. GC tablets significantly lower the elevated blood glucose level. In addition, they have antihyperlipidemic activity, hepatocellular protective role and restore the histology of the liver and pancreas.

Conclusion

GC tablets could be a promising alternative formulation to control the high blood glucose level in diabetic rats rather than chemically derivatized drugs.